Pericytes Stimulate Oligodendrocyte Progenitor Cell Differentiation during CNS Remyelination

The role of the neurovascular niche in CNS myelin regeneration is incompletely understood. Here, we show that, upon demyelination, CNS-resident pericytes (PCs) proliferate, and parenchymal non-vessel-associated PC-like cells (PLCs) rapidly develop. During remyelination, mature oligodendrocytes were...

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Main Authors: Alerie Guzman De La Fuente, Simona Lange, Maria Elena Silva, Ginez A. Gonzalez, Herbert Tempfer, Peter van Wijngaarden, Chao Zhao, Ludovica Di Canio, Andrea Trost, Lara Bieler, Pia Zaunmair, Peter Rotheneichner, Anna O’Sullivan, Sebastien Couillard-Despres, Oihana Errea, Maarja A. Mäe, Johanna Andrae, Liqun He, Annika Keller, Luis F. Bátiz, Christer Betsholtz, Ludwig Aigner, Robin J.M. Franklin, Francisco J. Rivera
Format: Article
Language:English
Published: Elsevier 2017-08-01
Series:Cell Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124717310951
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author Alerie Guzman De La Fuente
Simona Lange
Maria Elena Silva
Ginez A. Gonzalez
Herbert Tempfer
Peter van Wijngaarden
Chao Zhao
Ludovica Di Canio
Andrea Trost
Lara Bieler
Pia Zaunmair
Peter Rotheneichner
Anna O’Sullivan
Sebastien Couillard-Despres
Oihana Errea
Maarja A. Mäe
Johanna Andrae
Liqun He
Annika Keller
Luis F. Bátiz
Christer Betsholtz
Ludwig Aigner
Robin J.M. Franklin
Francisco J. Rivera
author_facet Alerie Guzman De La Fuente
Simona Lange
Maria Elena Silva
Ginez A. Gonzalez
Herbert Tempfer
Peter van Wijngaarden
Chao Zhao
Ludovica Di Canio
Andrea Trost
Lara Bieler
Pia Zaunmair
Peter Rotheneichner
Anna O’Sullivan
Sebastien Couillard-Despres
Oihana Errea
Maarja A. Mäe
Johanna Andrae
Liqun He
Annika Keller
Luis F. Bátiz
Christer Betsholtz
Ludwig Aigner
Robin J.M. Franklin
Francisco J. Rivera
author_sort Alerie Guzman De La Fuente
collection DOAJ
description The role of the neurovascular niche in CNS myelin regeneration is incompletely understood. Here, we show that, upon demyelination, CNS-resident pericytes (PCs) proliferate, and parenchymal non-vessel-associated PC-like cells (PLCs) rapidly develop. During remyelination, mature oligodendrocytes were found in close proximity to PCs. In Pdgfbret/ret mice, which have reduced PC numbers, oligodendrocyte progenitor cell (OPC) differentiation was delayed, although remyelination proceeded to completion. PC-conditioned medium accelerated and enhanced OPC differentiation in vitro and increased the rate of remyelination in an ex vivo cerebellar slice model of demyelination. We identified Lama2 as a PC-derived factor that promotes OPC differentiation. Thus, the functional role of PCs is not restricted to vascular homeostasis but includes the modulation of adult CNS progenitor cells involved in regeneration.
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spelling doaj.art-4a4c8209548f4d78bf8a35c0c107082d2022-12-22T00:13:55ZengElsevierCell Reports2211-12472017-08-012081755176410.1016/j.celrep.2017.08.007Pericytes Stimulate Oligodendrocyte Progenitor Cell Differentiation during CNS RemyelinationAlerie Guzman De La Fuente0Simona Lange1Maria Elena Silva2Ginez A. Gonzalez3Herbert Tempfer4Peter van Wijngaarden5Chao Zhao6Ludovica Di Canio7Andrea Trost8Lara Bieler9Pia Zaunmair10Peter Rotheneichner11Anna O’Sullivan12Sebastien Couillard-Despres13Oihana Errea14Maarja A. Mäe15Johanna Andrae16Liqun He17Annika Keller18Luis F. Bátiz19Christer Betsholtz20Ludwig Aigner21Robin J.M. Franklin22Francisco J. Rivera23Wellcome Trust and MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB20AH, UKInstitute of Molecular Regenerative Medicine, Paracelsus Medical University Salzburg, 5020 Salzburg, AustriaWellcome Trust and MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB20AH, UKWellcome Trust and MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB20AH, UKSpinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University Salzburg, 5020 Salzburg, AustriaWellcome Trust and MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB20AH, UKWellcome Trust and MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB20AH, UKWellcome Trust and MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB20AH, UKInstitute of Molecular Regenerative Medicine, Paracelsus Medical University Salzburg, 5020 Salzburg, AustriaSpinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University Salzburg, 5020 Salzburg, AustriaSpinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University Salzburg, 5020 Salzburg, AustriaSpinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University Salzburg, 5020 Salzburg, AustriaSpinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University Salzburg, 5020 Salzburg, AustriaSpinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University Salzburg, 5020 Salzburg, AustriaWellcome Trust and MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB20AH, UKDepartment of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, 751 85 Uppsala, SwedenDepartment of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, 751 85 Uppsala, SwedenDepartment of Neurosurgery, Tianjin Medical University General Hospital, Tianjin Neurological Institute, Key Laboratory of Post-Neuroinjury Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin 300052, ChinaDivision of Neurosurgery, Zürich University Hospital, Zürich University, 8091 Zürich, SwitzerlandLaboratory of Stem Cells and Neuroregeneration, Institute of Anatomy, Histology and Pathology, Faculty of Medicine, Universidad Austral de Chile, Valdivia, ChileDepartment of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, 751 85 Uppsala, SwedenInstitute of Molecular Regenerative Medicine, Paracelsus Medical University Salzburg, 5020 Salzburg, AustriaWellcome Trust and MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB20AH, UKWellcome Trust and MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB20AH, UKThe role of the neurovascular niche in CNS myelin regeneration is incompletely understood. Here, we show that, upon demyelination, CNS-resident pericytes (PCs) proliferate, and parenchymal non-vessel-associated PC-like cells (PLCs) rapidly develop. During remyelination, mature oligodendrocytes were found in close proximity to PCs. In Pdgfbret/ret mice, which have reduced PC numbers, oligodendrocyte progenitor cell (OPC) differentiation was delayed, although remyelination proceeded to completion. PC-conditioned medium accelerated and enhanced OPC differentiation in vitro and increased the rate of remyelination in an ex vivo cerebellar slice model of demyelination. We identified Lama2 as a PC-derived factor that promotes OPC differentiation. Thus, the functional role of PCs is not restricted to vascular homeostasis but includes the modulation of adult CNS progenitor cells involved in regeneration.http://www.sciencedirect.com/science/article/pii/S2211124717310951neurovascular nichepericytesremyelinationoligodendrocyte progenitor cellLama2
spellingShingle Alerie Guzman De La Fuente
Simona Lange
Maria Elena Silva
Ginez A. Gonzalez
Herbert Tempfer
Peter van Wijngaarden
Chao Zhao
Ludovica Di Canio
Andrea Trost
Lara Bieler
Pia Zaunmair
Peter Rotheneichner
Anna O’Sullivan
Sebastien Couillard-Despres
Oihana Errea
Maarja A. Mäe
Johanna Andrae
Liqun He
Annika Keller
Luis F. Bátiz
Christer Betsholtz
Ludwig Aigner
Robin J.M. Franklin
Francisco J. Rivera
Pericytes Stimulate Oligodendrocyte Progenitor Cell Differentiation during CNS Remyelination
Cell Reports
neurovascular niche
pericytes
remyelination
oligodendrocyte progenitor cell
Lama2
title Pericytes Stimulate Oligodendrocyte Progenitor Cell Differentiation during CNS Remyelination
title_full Pericytes Stimulate Oligodendrocyte Progenitor Cell Differentiation during CNS Remyelination
title_fullStr Pericytes Stimulate Oligodendrocyte Progenitor Cell Differentiation during CNS Remyelination
title_full_unstemmed Pericytes Stimulate Oligodendrocyte Progenitor Cell Differentiation during CNS Remyelination
title_short Pericytes Stimulate Oligodendrocyte Progenitor Cell Differentiation during CNS Remyelination
title_sort pericytes stimulate oligodendrocyte progenitor cell differentiation during cns remyelination
topic neurovascular niche
pericytes
remyelination
oligodendrocyte progenitor cell
Lama2
url http://www.sciencedirect.com/science/article/pii/S2211124717310951
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